Table 1

 Twelve different truncating NPHP6/CEP290 mutations found in 6 families with JBTS and 2 families with SLSN

Family (individual)Country of originNucleotide alteration(s)*Alteration(s) in coding sequenceExon (segregation)**Parental consanguinityAge at ESRD‡ (years)PhenotypeOcular features (age of diagnosis, years)Central nervous system features (other)
?, Second mutation not found; AT, ataxia; CA, congenital amaurosis (bilateral); CVA, cerebellar vermis aplasia/hypoplasia; ESRD, end-stage renal disease; het, heterozygous in affected individual; hom, homozygous in affected individual; LCA, Leber congenital amaurosis (blindness within the first 2 years of life); JBTS, diagnosed with Joubert syndrome; M, mutation identified in mother; MEC, occipital menigoencephalocele; MR, mental retardation/psychomotor retardation; Mwt maternal sequence is wild type; ND, no data or DNA available; NY, nystagmus; P, mutation identified in father; Pwt paternal sequence is wild type; SLSN, diagnosed with Senior–Løken syndrome; RC, retinal coloboma; TRD, tapetoretinal degeneration.
*All mutations were absent from at least 188 chromosomes of healthy controls.
‡All patients had renal ultrasonography results compatible with nephronophthisis (increased echogenicity and/or corticomedullary cysts).
§Renal function significantly reduced.
¶This patient is also known to have a heterozygous missense mutation in the NPHP4 gene (C1880T, T627M).28
**Previously published.23,25,26
A372 (II-1, II-2)ItalyC3811T**R1271X**32 (het, P)NDJBTSLCA, RC (ND)MR
5734delT**W1912fsX1923**43 (het, M)
A989 (II-1)SwitzerlandC4882T**Q1628X**38 (het, ND)5JBTSLCA, NYCVA, MR, spastic paresis, liver fibrosis
G5941T**E1981X,**44 (het, ND)
F101 (II-2)USA1066-1G>Asplice site13 (het, P)9JBTSLCA (5 months)MR, empty sella, hypoplasia of the optic chiasm, hypothalamic hypoplasia, (breathing, abnormality, pes planus)
5163delT**T1721fsX1723**39 (het, Pwt, M ND)Empty sella
F57 (II-1)GermanyA1G, 1419-1423del AATAAStart codon defect2 (start codon) (het, ND)24SLSNNY, early-onset TRD keratoconus, vision <1 (early childhood)Complex focal seizures (hyperlipidaemia, scoliosis)
K473fsX47815 (het, ND)
F122 (II-2)GermanyT2249G,?**L750X, ?23 (het, M)>6§JBTSLCA, NYCVA, AT, MR
A1332 (II-1)Syria164_167del CTCA, ?T55fsX57, ?3 (het, ND)+None at 1.5JBTSLCA, NYCVA, MR
F938 (II-1)Bosnia3104-2A>G,?Splice site, ?29 (het, M)13JBTSNY, esotropia, retinal dystrophy (14)MR, hypotonia (scoliosis)
F848 (II-1)¶ItalyC5932T,?R1978X, ?44 (het, ND)40SLSNTRD (vision 1/10 at 44)ND